Evidence for contribution of CD4+ CD25+ regulatory T cells in maintaining immune tolerance to human factor IX following perinatal adenovirus vector delivery

Journal of Immunology Research
Megha NivsarkarSimon Waddington

Abstract

Following fetal or neonatal gene transfer in mice and other species immune tolerance of the transgenic protein is frequently observed; however the underlying mechanisms remain largely undefined. In this study fetal and neonatal BALB/c mice received adenovirus vector to deliver human factor IX (hFIX) cDNA. The long-term tolerance of hFIX was robust in the face of immune challenge with hFIX protein and adjuvant but was eliminated by simultaneous administration of anti-CD25+ antibody. Naive irradiated BALB/c mice which had received lymphocytes from donors immunised with hFIX developed anti-hFIX antibodies upon immune challenge. Cotransplantation with CD4+CD25+ cells isolated from neonatally tolerized donors decreased the antibody response. In contrast, cotransplantation with CD4+CD25- cells isolated from the same donors increased the antibody response. These data provide evidence that immune tolerance following perinatal gene transfer is maintained by a CD4+CD25+ regulatory population.

References

Oct 22, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Feng ZhangThomas M Aune
Apr 27, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Simon N WaddingtonJesus Prieto
Feb 13, 2008·Cell·Simon N WaddingtonAndrew H Baker
Jul 13, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ahad A RahimSimon N Waddington
May 23, 2012·Advances in Immunology·Jeff E Mold, Joseph M McCune

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Citations

Oct 29, 2015·American Journal of Respiratory and Critical Care Medicine·Dragana VidovićZeger Debyser
Jul 4, 2015·Scientific Reports·Suzanne M K BuckleyTristan R McKay
Jan 16, 2019·Gene Therapy·Rajvinder KardaSimon N Waddington
Jul 18, 2018·Nature Medicine·Giulia MassaroAhad A Rahim
Feb 9, 2020·Scientific Reports·Rajvinder KardaSimon N Waddington

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Methods Mentioned

BETA
transgenic
ELISA
PCR
FACS
Assay

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